Family history of cancer and the risk of bladder cancer: A case–control study from Italy

BackgroundA family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear.MethodsWe analyzed data from an Italian case–control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling’s number.ResultsThe OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02–4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91–4.32) after additional adjustment for smoking and siblings’ number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65 years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR = 2.97, 95%CI 1.35–6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk.ConclusionThis study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system.     

Evaluation of the sensitivity of a medical data-mining application to the number of elements in small databases

Data-mining methods can be used to generate rules, or identify patterns, from medical data to assist clinical diagnosis and decision-making. However, in the initial stages of a clinical study on a new diagnostic approach, there could be a limited medical dataset available; or the medical characteristics could mean that the number of patients involved in the study will never be large. Diagnoses made using the rules discovered from such small medical databases should be considered suspect unless a confidence range for a particular diagnosis can be established. A method to evaluate the sensitivity and reliability of data-mining with small databases is presented in this paper. Efron's bootstrap method for statistical testing was used to assess the accuracy of the rules produced during the training step of the data-mining algorithm. The case study for validating this new approach was based on a limited-sized mammographic database previously used to discover associations between the diagnostic features of breast masses in mammograms and the biopsy-based classification of the masses. Using the new approach, it was possible to distinguish between the association rules that were sensitive to the size of the training datasets from those that were not. The methods proposed should lead to an efficient way for validating the patterns discovered in medical data-mining applications using small datasets.     

Allergic diseases and asthma in the family predict the persistence and onset-age of asthma: a prospective cohort study

BackgroundFamily history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood.MethodsWe assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991–2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs.ResultsFamily history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80).ConclusionsFamily history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history.     

Endogenous estrogen, testosterone and progesterone levels in relation to breast cancer risk

Multiple lines of evidence support a central role of hormones in the etiology of breast cancer. In epidemiologic studies, considerable effort has focused on delineating the role of endogenous hormones in risk of breast cancer among postmenopausal women. Recently, substantial additional data has accrued from prospective studies where endogenous hormones are measured in study subjects prior to disease diagnosis. In this review, the epidemiologic evidence linking sex steroids—estrogens, testosterone, and progesterone, specifically—with subsequent risk of breast cancer in both premenopausal and postmenopausal women is summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two- to three-fold higher risk of breast cancer. Evidence among premenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. However, both positive and null associations have been observed with estrogens and progesterone and clearly more evaluation is needed.     

前瞻研究中多因素人群归因危险度的Poisson回归模型估计

本文提出多因素前瞻研究中利用Poisson回归发病率预测模型和相对危险度估计调整和综合人群归因危险度的方法,与Bruzzi等和Deubner等提出的多因素人群归因危险度估计方法进行了比较,强调在前瞻资料的人群归因危险度的估计中利用poisson回归模型考虑失访病例和随访时间效应,并能直接估计相对危险度的优势.应用所建立的方法对启东县肝病人群14年前瞻观察资料进行肝癌危险因素的人群归因危险度的估计。     

Reproductive effort and growth in the prosobranch snail,Viviparus ater

Summary We compared two populations of Viviparus ater from Lake Zürich and Lake Maggiore with respect to the reproductive investment of individual females throughout their lives. Based on field observations of the bumber and size of offspring and from measurements of the differences between growth rings on the shells we constructed a probabilistic model for the life history of the females. A simulation showed that the overall productivity of females was higher in Lake Zürich than in Lake Maggiore. The higher productivity of females in Lake Zürich was due to faster growth before maturity and higher fecundity after maturity. The reproductive effort, as measured by the percentage of assimulated energy used for reproduction, remained constant throughout the life of the females in Lake Zürich, whereas it declined with age in Lake Maggiore. We interpret this as the outcome of a reproductive strategy that avoids risks due to reckless reproduction, rather than as two different strategies which have been selected in response to different habitat types.     

Mechanical phenotype is important for stromal aromatase expression

Evidence that aromatase expression in tumor-associated breast stroma is elevated, provides a rationale for use of aromatase inhibitors (AIs) in breast cancer treatment. However, regulation of local aromatase expression in cancer-free breast stroma is poorly understood. Recent clinical work indicates that stromal cells in dense breast tissue tend to express higher levels of aromatase than their counterpart from non-dense tissue. Consistent with the clinical observation, our cell culture-based study indicated that cell density, cell shape, and extracellular matrix (ECM) significantly induced stromal aromatase expression via a distinct signal transduction pathway. In addition, we identified a number of cell surface markers that are commonly associated with aromatase-expressing stromal cells. As mammographic density is one of the strongest and most prevalent risk factors for breast cancer, these findings provide a potential mechanistic link between alterations in tissue composition of dense breast tissue and increased stromal aromatase expression. Further exploration of the in vitro model system may advance understanding of an important problem in breast cancer biology.